Ethyl Acetoacetate → 5-fluoro-2-methyl-8-propoxy-1H-quinolin-4-one

HRID 238324Notes

Reaction equation

HRID 238324 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:9][CH2:10][CH2:11][CH3:12])=[C:6]([CH:8]=1)[NH2:7].[C:13](OCC)(=[O:18])[CH2:14][C:15]([CH3:17])=O>C1C=CC=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:9][CH2:10][CH2:11][CH3:12])=[C:6]2[C:8]=1[C:13](=[O:18])[CH:14]=[C:15]([CH3:17])[NH:7]2

Participants

4

Reactant 2

HCID 8868Ethyl AcetoacetateHCID 261896335-Fluoro-2-propoxyaniline

Product 1

HCID 669172845-fluoro-2-methyl-8-propoxy-1H-quinolin-4-oneYield 43.2%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

Amberlyst 15 (1.0 g, a product of Sigma Aldrich Corp.) was added to a benzene solution (200 ml) of 5-fluoro-2-propoxyaniline (10 g, 59 mmol) and ethyl acetoacetate (7.7 g, 59 mmol). The mixture was stirred while heating under reflux for 6 hours and using a Dean-Stark trap. The reaction mixture was cooled to room temperature, the resin was removed by filtration, and the filtrate was concentrated under reduced pressure. Diphenyl ether (20 ml) was added to the residue. The mixture was heated using a mantle heater and stirred under reflux for 2 hours. After the reaction mixture was cooled to room temperature, insoluble matter obtained by the addition of n-hexane-ethyl acetate (2:1) was collected by filtration. The substance remaining on the filter was washed with n-hexane-ethyl acetate (2:1), and dried to thereby obtain 6.0 g of powdery pale yellow 5-fluoro-2-methyl-8-propoxy-1H-quinolin-4-one (yield: 43%).

Workup

  1. temperaturewhile heating
  2. temperatureunder reflux for 6 hours
  3. customthe resin was removed by filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. additionDiphenyl ether (20 ml) was added to the residue
  6. temperatureThe mixture was heated
  7. stirringstirred
  8. temperatureunder reflux for 2 hours
  9. temperatureAfter the reaction mixture was cooled to room temperature
  10. custominsoluble matter obtained by the addition of n-hexane-ethyl acetate (2:1)
  11. filtrationwas collected by filtration
  12. washwas washed with n-hexane-ethyl acetate (2:1)
  13. customdried

Sources & evidence

ORD record
ord-c0712aff78694c4faeb699342c3da49a
Source dataset
uspto-grants-2014_02
Patent number
US08642619B2

Reaction notes

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